Viral vulnerability

Persistent viral infection, even those that are undetectable or asymptomatic, can cause some cancers and contribute to their severity. Viracta Therapeutics Inc. is treating virus-associated cancers by forcing them to re-express latent viral proteins that make cancerous cells vulnerable to antiviral treatment.

In November, Viracta acquired lead program VRx-3996 from Chroma Therapeutics Ltd. in exchange for an undisclosed equity stake. Chroma had been studying the HDAC inhibitor in Phase Ib testing to treat solid tumors but sold it to Viracta because its efficacy was not great enough to raise funds for its development, according to Viracta CBO David Slack.Viracta will combine it with the nucleoside analog prodrug valganciclovir to treat Epstein-Barr virus (EBV)-positive lymphoma, and possibly to treat nasopharyngeal carcinoma and gastric carcinomas and for prophylaxis of post-transplant lymphoproliferative disease (PTLD).

VRx-3996 induces EBV to express the thymidine kinase enzyme. The enzyme in turn catalyzes the addition of a phospate group to nucleoside antivirals - the initial step in activating valganciclovir after first-pass metabolism. Non-specific intracellular kinases then add a second and a third phosphate to form the active triphosphate form of the drug, which inhibits viral DNA synthesis.

“You need to hit certain HDACs, and we know which ones to hit to turn on certain viral...